GC2 Antibody

Mechanism of Action: Blocking Complement Immune Evasion

HSV-2 gC2 binds to complement C3b, preventing its deposition on viral particles and infected cells. This interaction inhibits complement-mediated neutralization and lysis . GC2 Antibody counteracts this by:

• Blocking C3b binding: Antibodies generated through immunization with gC2 subunit antigens (e.g., with CpG/alum adjuvants) prevent gC2-C3b interactions, restoring complement activation .

• Enhancing antibody-mediated neutralization: In combination with complement, GC2 Antibody amplifies virus neutralization by enabling C3b deposition and subsequent immune clearance .

Comparative Efficacy in Natural Infection vs. Vaccination

GC2 Antibody in Multivalent Vaccine Strategies

GC2 Antibody is often combined with other antigens (e.g., gD2 for entry inhibition, gE2 for Fc receptor blocking) to target multiple viral evasion mechanisms:

Trivalent gC2/gD2/gE2 Vaccine

• Efficacy:

  • Neutralization: 2.4–4.4 log₁₀ reduction in viral titer with complement .

  • Protection: 97% dorsal root ganglion (DRG) protection in mice, preventing latency .

  • Synergy: gC2 + gE2 antibodies block both complement and Fc-mediated evasion, enhancing neutralization by 2 log₁₀ .

Key Discoveries

1. Human Antibody Limitations:

   • 8/10 HSV-2-infected individuals produced non-blocking gC2 antibodies despite high titers .

   • Only high-titer sera (e.g., >1:20 dilution) showed partial blocking .

2. Guinea Pig Models:

   • Vaccination with gC2 (CpG/alum) induced antibodies that blocked C3b binding more effectively than natural infection .

   • Trivalent vaccines reduced vaginal HSV-2 DNA shedding by 0.8–1.7 log₁₀ in mice .

3. Synergy with gE2:

   • Combined gC2 + gE2 antibodies neutralized HSV-2 more effectively than single antibodies, especially with complement .

Unresolved Questions

• Cross-Species Variability: Human vs. animal antibody responses differ in blocking efficiency .

• Adjuvant Optimization: CpG/alum outperforms other adjuvants in inducing functional GC2 Antibody .

• Latency Prevention: While DRG protection is achieved, complete latency eradication remains unattained .